[Show abstract][Hide abstract]ABSTRACT: To determine the effectiveness of enzyme replacement therapies (ERT) for children with Gaucher disease (GD).
A longitudinal cohort study including prospective and retrospective clinical data. Age- and gender-adjusted treatment effects were estimated using generalised linear mixed models. Children on treatment contributed data before and during treatment. Children not on treatment contributed natural history data.
Consenting children (N = 25, aged 1.1 to 15.6 years) with a diagnosis of GD (14 with GD1 and 11 with GD3) who attended a specialist treatment centre in England. At recruitment, 24 patients were receiving ERT (mean treatment duration, 5.57 years; range 0-13.7 years).
Clinical outcomes chosen to reflect disease progression, included platelet count; haemoglobin and absence/presence of bone pain.
Duration of ERT was associated with statistically significant improvements in platelet count (p < 0.001), haemoglobin (p < 0.001), and reported bone pain (p = 0.02). The magnitude of effect on haematological parameters was greater in children with GD3 than in those with GD1.
These data provide further evidence of the long-term effectiveness of ERT in children with GD.

[Show abstract][Hide abstract]ABSTRACT: Long-term complications and associated conditions of type 1 Gaucher Disease (GD) can include splenectomy, bone complications, pulmonary hypertension, Parkinson disease and malignancies. Enzyme replacement therapy (ERT) reverses cytopenia and reduces organomegaly. To study the effects of ERT on long-term complications and associated conditions, the course of Gaucher disease was modelled.The cohort consisted of all diagnosed GD patients in the Netherlands. Mutually exclusive disease states were defined as `asymptomatic¿, `signs/symptoms¿, `recovery¿, `splenectomy¿, `bone complication¿, `multiple complications¿ and `malignancy¿. A natural history (NH) cohort was delineated based upon historical data on Dutch patients before ERT was available. Cumulative incidence curves were composed for progression from each disease state to the next. Two scenarios were applied for the ERT cohort: time to complications was calculated from A. start of ERT; B. entering the previous disease state.Median time for the development of signs and/or symptoms was 30.1 years (N = 73). In the NH cohort (N = 42), 9% had developed a bone complication after 10 years in the signs/symptoms phase, while 21% had undergone a splenectomy. In the ERT cohort (N = 29 (A), N = 28 (B)), 12% (A) or 4% (B) had developed a bone complication after 10 years in this phase and no patient was splenectomized. No patients in the NH cohort recovered, compared to 50% in the ERT cohort after 3.6 years (N = 28 (A)) or 22.4 years (N = 27 (B)) of treatment. Median time from a first to a second complication was 11 years in the NH cohort (N = 31), whereas 16 respectively 14 percent had developed a second complication after 10 years in the ERT cohort (N = 17, scenario A/B). Fourteen percent (scenario A/B) developed an associated malignancy after 10 years in the phase `multiple complications¿ (N = 23). Associated malignancies occurred almost exclusively in advanced disease stages, therefore it is suggested that ERT reduces their incidenceLong-term ERT for GD can reduce the incidence of splenectomy and bone complications. As ERT prevents progression to more advanced stages of GD it will most likely result in a reduction of associated malignancies.

[Show abstract][Hide abstract]ABSTRACT: To evaluate the cost-effectiveness of enzyme replacement therapy (ERT) compared to standard medical care without ERT in the Dutch cohort of patients with type 1 Gaucher disease (GD I).
Cost-effectiveness analysis was performed using a life-time state-transition model of the disease's natural course. Transition probabilities, effectiveness data and costs were derived from retrospective data and prospective follow-up of the Dutch study cohort.Setting: The tertiary referral center for Gaucher disease in the Netherlands.Participants: The Dutch cohort of patients with GD I.Intervention: ERT versus standard medical care without ERT in symptomatic patients.Main outcome measures: Years free of end organ damage (YFEOD) (splenectomy, bone complication, malignancy, multiple complications), quality adjusted life years (QALY), and costs.
Over an 85 year lifetime, an untreated GD I patient will generate 48.9 YFEOD and 55.86 QALYs. Starting ERT in a symptomatic patient increases the YFEOD by 12.8 years, while the number of QALYs gained increases by 6.27. The average yearly ERT medication costs range between [euro sign]124,000 and [euro sign]258,000 per patient. The lifetime costs of ERT starting in the symptomatic stage are [euro sign]5,716,473 against [euro sign]171,780 without ERT, a difference of [euro sign]5,544,693. Consequently, the extra costs per additional YFEOD or per additional QALY are [euro sign]434,416 and [euro sign]884,994 respectively. After discounting effects by 1.5% and costs by 4% and under a reasonable scenario of ERT unit cost reduction by 25%, these incremental cost-effectiveness ratios could decrease to [euro sign]149,857 and [euro sign]324,812 respectively.
ERT is a highly potential drug for GD I with substantial health gains. The conservatively estimated incremental cost-effectiveness ratios are substantially lower than for Pompe and Fabry disease. We suggest that the high effectiveness has contributed importantly to acceptance of reimbursement of ERT for GD I. The present study may further support discussions on acceptable price limits for ultra-orphan products.

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